Dengue viruses are a leading cause of morbidity and mortality throughout the tropics and subtropics. The estimate is that more than 100 million people in the tropics are infected annually by this virus. This threat has now reached the southern United States with the arrival of the Aedes albopictus mosquito vector.Attempts to develop live attenuated dengue vaccines analogous to the yellow fever vaccine have yet to be successful. The proposal is research directed toward development of a defined subunit dengue vaccine using yeast virus-like particles (VLPs) fused to peptides of the dengue envelope (E) glycoprotein. Such self- assembling VLPs are comprised of the protein product, p1, of the TYA gene of the yeast transposable element Ty. Fusion of dengue E cDNA fragments to the TYa gene will produce p1-dengue fusion proteins. The resulting hybrid VLPs will require a single ultracentrifugation step for purification and should present epitopes in a highly immunogenic form. During phase I, the feasibility of this approach will be tested by constructing a yeast TYA:dengue envelope peptide fusion gene and testing expression, formation of hybrid VLPs, and immunoreactivity of the hybrid VLPs.